Allogeneic hematopoietic stem cell transplant (HSCT) is the only curative therapy for many malignances and many non-malignant disorders, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. Noninfectious lung injury, or idiopathic pneumonia syndrome (IPS), remains a significant contributor to morbidity and mortality after transplant. Our laboratory has demonstrated that both cellular and soluble effectors (including TNFα) contribute to the development of IPS. Our lab continues to be interested in identifying additional mediators of lung inflammation that may be contributing to lung injury and endothelial cell apoptosis, activation, and leak during IPS, and several pathways have been identified for further exploration. Further elucidation of these pathways and their interdependence can provide insight into IPS development and lead to potential therapeutic targets. Post-Transplant Cyclophosphamide is a GVHD regimen pioneered at Hopkins that has greatly expanded the donor pool, allowing us to offer HSCT to patients who previously may not have been candidates. For non-malignant disorders, reducing the prep regimen intensity while preserving engraftment has been the major hurdle in treating these patients with HSCT. Using a reduced-intensity regimen and an alternative donor with post-transplant cyclophosphamide for GVHD prophylaxis has proven very successful in the first series of patients we have treated with this protocol. My goal is to create a prospective trial to treat all of these patients with a standard regimen in order to improve engraftment and reduce toxicity in this patient population.